Stat5 is a transcriptional activator and repressor utilized by many cytokine receptors. Our data indicate that Stat5 is a critical component of IL-3- and SCF-mediated cell survival, proliferation, and cytokine production. The current proposal will elaborate the molecular mechanisms by which Stat5 controls these processes. Gain-of-function mutations in the SCF receptor, c-kit, are known to contribute to neoplasia, and correlate with a failure to undergo cytokine-induced apoptosis. We hypothesize that these features can be explained at least partly by constitutive Stat5 activation. This proposal will assess the contribution of Stat5 to cytokine-mediated cell survival, proliferation, cytokine production, and neoplastic transformation. As such, the resulting data will be important to the understanding and treatment of cancer.